Pulmonary dendritic cells and alveolar macrophages are regulated by γδ T cells during the resolution of S. pneumoniae-induced inflammation

γδ T cells commonly associate with mucosal and epithelial sites, fulfilling a variety of immunoregulatory functions. While lung γδ T cells have well-characterized pro-inflammatory activity, their potential role in the resolution of lung inflammation has yet to be explored in any detail. Indeed, given the importance of minimizing inflammation, the cellular mechanisms driving the resolution of lung inflammation are poorly understood. Using a murine model of acute Streptococcus pneumoniae-mediated lung inflammation, we now show that resolution of inflammation following bacterial clearance is associated with a > 30-fold increase in γδ T-cell number. Although inflammation eventually resolves in TCRδ−/− mice, elevated numbers of alveolar macrophages and pulmonary dendritic cells, and the appearance of well-formed granulomas in lungs of TCRδ−/− mice, together indicated a role for γδ T cells in regulating mononuclear phagocyte number. Ex vivo, both alveolar macrophages and pulmonary dendritic cells were susceptible to lung γδ T cell-mediated cytotoxicity, the first demonstration of such activity against a dendritic cell population. These findings support a model whereby expansion of γδ T cells helps restore mononuclear phagocyte numbers to homeostatic levels, protecting the lung from the consequences of inappropriate inflammation. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd

Light scalars: Coherent nonlinear Thomson scattering and detection

Several theories of beyond-the-standard-model physics predict light scalars that couple to fermions. By extending classical electrodynamics to include an electron-scalar coupling, we calculate the nonlinear Thomson scattering of light scalars in the collision of an electron with a monochro- matic electromagnetic background. In doing so, we identify the classical electron-scalar current, which allows for straightforward inclusion of the process in laser-plasma particle-in-cell simulations. Scattering of pseudoscalar particles is found to vanish in the classical (or, equivalently, the low-lightfront-momentum) limit. When electrons co-propagate with the laser pulse, we demonstrate that coherence effects in the production of light scalar particles can greatly enhance the signal for sub-eV scalars. When the electron beams counter-propagate with the laser pulse, we demon- strate that experiments can probe larger scalar masses due to the larger momentum transfer in the collisions. We then discuss a possible lab-based experimental set-up to detect this scalar signal which is similar to light-shining-through-the-wall experiments. Using existing experimental facilities as benchmarks, we calculate projected exclusion bounds on the couplings of light scalars in such experiments

Distinct contributions of DNA methylation and histone acetylation to the genomic occupancy of transcription factors

Epigenetic modifications on chromatin play important roles in regulating gene expression. Although chromatin states are often governed by multilayered structure, how individual pathways contribute to gene expression remains poorly understood. For example, DNA methylation is known to regulate transcription factor binding but also to recruit methyl-CpG binding proteins that affect chromatin structure through the activity of histone deacetylase complexes (HDACs). Both of these mechanisms can potentially affect gene expression, but the importance of each, and whether these activities are integrated to achieve appropriate gene regulation, remains largely unknown. To address this important question, we measured gene expression, chromatin accessibility, and transcription factor occupancy in wild-type or DNA methylation-deficient mouse embryonic stem cells following HDAC inhibition. We observe widespread increases in chromatin accessibility at retrotransposons when HDACs are inhibited, and this is magnified when cells also lack DNA methylation. A subset of these elements has elevated binding of the YY1 and GABPA transcription factors and increased expression. The pronounced additive effect of HDAC inhibition in DNA methylation-deficient cells demonstrates that DNA methylation and histone deacetylation act largely independently to suppress transcription factor binding and gene expression

Phosphorylation induces structural changes in the Autographa californica nucleopolyhedrovirus P10 protein

Baculoviruses encode a variety of auxiliary proteins that are not essential for viral replication but provide them with a selective advantage in nature. P10 is a 10 kDa auxiliary protein produced in the very-late phase of gene transcription by Autographa californica multiple nucleopolyhedrovirus (AcMNPV). The P10 protein forms cytoskeletal-like structures in the host cell that associate with microtubules varying from filamentous forms in the cytoplasm to aggregated peri-nuclear tubules that form a cage-like structure around the nucleus. These P10 structures may have a role in the release of occlusion bodies (OBs) and thus mediate horizontal transmission of the virus between insect hosts. Here it is demonstrated, using mass spectrometric analysis, that the C-terminus of P10 is phosphorylated during virus infection of cells in culture. Analysis of the P10 mutants encoded by recombinant baculoviruses in which putative phosphorylation residues were mutated to alanine showed that serine 93 is a site of phosphorylation. Confocal microscopy examination of the serine 93 mutant structures revealed an aberrant formation of the peri-nuclear tubules. Thus, phosphorylation of serine 93 may induce aggregation of filaments to form tubules. Together, these data suggest that the phosphorylation of serine 93 affects P10 structural conformation. IMPORTANCE The baculovirus P10 protein has been researched intensively since it was first observed in 1969, but its role during the viral infection remains unclear. It is conserved in the alphabaculoviruses and expressed at high levels during virus infection. Producing large amounts of a protein is wasteful for the virus unless it is advantageous for survival of its progeny and therefore P10 presents an enigma. As P10 polymerises to form organised cytoskeletal structures that co-localise with the host cell microtubules, the structural relationship of the protein with the host cell may present a key to help understand the function and importance of this protein. This study addresses the importance of the structural changes in P10 during infection and how they may be governed by phosphorylation. The P10 structures affected by phosphorylation are closely associated with the viral progeny and thus, potentially, be responsible for its dissemination and survival

Molecular and electronic structure of terminal and alkali metal-capped uranium(V) nitride complexes

Determining the electronic structure of actinide complexes is intrinsically challenging because inter-electronic repulsion, crystal field, and spin–orbit coupling effects can be of similar magnitude. Moreover, such efforts have been hampered by the lack of structurally analogous families of complexes to study. Here we report an improved method to U≡N triple bonds, and assemble a family of uranium(V) nitrides. Along with an isoelectronic oxo, we quantify the electronic structure of this 5f1 family by magnetometry, optical and electron paramagnetic resonance (EPR) spectroscopies and modelling. Thus, we define the relative importance of the spin–orbit and crystal field interactions, and explain the experimentally observed different ground states. We find optical absorption linewidths give a potential tool to identify spin–orbit coupled states, and show measurement of UV···UV super-exchange coupling in dimers by EPR. We show that observed slow magnetic relaxation occurs via two-phonon processes, with no obvious correlation to the crystal field

China’s rising hydropower demand challenges water sector

Demand for hydropower is increasing, yet the water footprints (WFs) of reservoirs and hydropower, and their contributions to water scarcity, are poorly understood. Here, we calculate reservoir WFs (freshwater that evaporates from reservoirs) and hydropower WFs (the WF of hydroelectricity) in China based on data from 875 representative reservoirs (209 with power plants). In 2010, the reservoir WF totaled 27.9 × 109 m3 (Gm3), or 22% of China’s total water consumption. Ignoring the reservoir WF seriously underestimates human water appropriation. The reservoir WF associated with industrial, domestic and agricultural WFs caused water scarcity in 6 of the 10 major Chinese river basins from 2 to 12 months annually. The hydropower WF was 6.6 Gm3 yr−1 or 3.6 m3 of water to produce a GJ (109 J) of electricity. Hydropower is a water intensive energy carrier. As a response to global climate change, the Chinese government has promoted a further increase in hydropower energy by 70% by 2020 compared to 2012. This energy policy imposes pressure on available freshwater resources and increases water scarcity. The water-energy nexus requires strategic and coordinated implementations of hydropower development among geographical regions, as well as trade-off analysis between rising energy demand and water use sustainability

The inverse-trans-influence in tetravalent lanthanide and actinide bis(carbene) complexes

Across the periodic table the trans-influence operates, whereby tightly bonded ligands selectively lengthen mutually trans metal–ligand bonds. Conversely, in high oxidation state actinide complexes the inverse-trans-influence operates, where normally cis strongly donating ligands instead reside trans and actually reinforce each other. However, because the inversetrans-influence is restricted to high-valent actinyls and a few uranium(V/VI) complexes, it has had limited scope in an area with few unifying rules. Here we report tetravalent cerium, uranium and thorium bis(carbene) complexes with trans C¼M¼C cores where experimental and theoretical data suggest the presence of an inverse-trans-influence. Studies of hypothetical praseodymium(IV) and terbium(IV) analogues suggest the inverse-trans-influence may extend to these ions but it also diminishes significantly as the 4f orbitals are populated. This work suggests that the inverse-trans-influence may occur beyond high oxidation state 5f metals and hence could encompass mid-range oxidation state actinides and lanthanides. Thus, the inverse-trans-influence might be a more general f-block principle

Fundamental Strings, Holography, and Nonlinear Superconformal Algebras

We discuss aspects of holography in the AdS_3 \times S^p near string geometry of a collection of straight fundamental heterotic strings. We use anomalies and symmetries to determine general features of the dual CFT. The symmetries suggest the appearance of nonlinear superconformal algebras, and we show how these arise in the framework of holographic renormalization methods. The nonlinear algebras imply intricate formulas for the central charge, and we show that in the bulk these correspond to an infinite series of quantum gravity corrections. We also makes some comments on the worldsheet sigma-model for strings on AdS_3\times S^2, which is the holographic dual geometry of parallel heterotic strings in five dimensions.Comment: 25 page

Influence of irrigant needle depth in removing bioluminescent bacteria inoculated into instrumented root canals using real-time imaging in vitro

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73506/1/j.1365-2591.2004.00906.x.pd

Paedomorphic facial expressions give dogs a selective advantage

How wolves were first domesticated is unknown. One hypothesis suggests that wolves underwent a process of self-domestication by tolerating human presence and taking advantage of scavenging possibilities. The puppy-like physical and behavioural traits seen in dogs are thought to have evolved later, as a byproduct of selection against aggression. Using speed of selection from rehoming shelters as a proxy for artificial selection, we tested whether paedomorphic features give dogs a selective advantage in their current environment. Dogs who exhibited facial expressions that enhance their neonatal appearance were preferentially selected by humans. Thus, early domestication of wolves may have occurred not only as wolf populations became tamer, but also as they exploited human preferences for paedomorphic characteristics. These findings, therefore, add to our understanding of early dog domestication as a complex co-evolutionary process